This application, from Cincinnati Children's Hospital Medical Center, is a competing continuation of our existing P60 Multidisciplinary Clinical Research Center grant and is complementary to our ongoing P30 Cincinnati Rheumatic Diseases Core Center grant. The Center's chief focus is a greater understanding of the mechanisms of the rheumatic illnesses of childhood and their treatment. Special emphasis is given to cross-disciplinary interactions, and leveraging of resources such that synergism is realized. Four projects (none of which are pilot projects) are proposed. The titles and chief foci of each are given below. 1) Improved Diagnostic and Advanced Magnetic Resonance Imaging for Pediatric Neuro-Psychiatric SLE (NPSLE). Chief aims of this project are to develop an easy-to-use screening tool for neuro-cognitive dysfunction (NCD) that can be utilized in the routine clinic setting, and to determine the utility of advanced imaging techniques to heighten our understanding of how pediatric SLE affects the CMS, resulting in NCD. 2) Improved Understanding of the Biology and Use of TNF Inhibition in juvenile idiopathic arthritis (JIA). The primary goal of this study is to develop methods to accurately identify those children in whom anti-TNF therapies can be safely stopped after a favorable response, without risk of a rapid disease flare. This study will result in a better understanding of the effect of TNF antagonist therapy on the biology of JIA and a safer and more cost effective approach to the use of these profoundly important new therapies. 3) Macrophage Activation Syndrome (MAS) Biomarkers in Systemic JIA (sJIA). This project will investigate whether polymorphisms in the MUNC 13-4 gene contribute to the predisposition to MAS, thereby helping to identify children at an elevated increased risk of MAS. Preliminary evidence suggests that serum levels of slL2Ra and sCD163 may reflect the degree of activation and expansion of T cells and macrophages in MAS, and thus serve as early diagnostic markers. Further, we will investigate whether elevated levels of these soluble receptors can distinguish reliably between those with overt and sub-clinical MAS from those with conventional sJIA flare. We will determine if those at increased risk of MAS represent a distinct subtype of sJIA which can be recognized at onset of sJIA. 4) Determinants of Health-Related Quality of Life in Children with JIA. The chief aim of this project is to determine the pathways by which medical variables (biological, physiological, clinical) and non-medical variables (child, family, environmental) predict the HRQOL in children being treated for JIA. A well-matured Methodology Core will serve all four MCRC projects, as well as many projects in the research base, and serves as a national and international resource. An Administrative Unit, composed of several internal and external advisory boards, will exercise administrative and operational oversight. [unreadable]